Condensation of aminoaromatic compounds with carbohydrates and related materials



2,926,177 Patented Feb. 23, 1960 ice CONDENSATION F AMINOAROMATIC COM-POUNDS WITH CARBOHYDRATES AND RE- LATED MATERIAL? No Drawing.Application June 18, 1957 Serial No. 666,485

5 Claims. (Cl. 260-6453) This application is a continuation-in-part ofmy copending application Serial No. 401,068, filed December 29, 1953,now Patent No. 2,798,079.

This invention relates to a process for interacting aminoaromaticcompounds with carbohydrates and materials closely related tocarbohydrates. The process relates more particularly to the condensationof simple sugars, their desoxyand omega-carboxy derivatives, compoundsugars or oligosaccharides, and polysaccharides with aminoaromaticcompounds in the presence of a hydrogen fluoride catalyst.

An object of this invention is to produce organic materials suitable foruse per se or as intermediates in the manufacture of detergents,pharmaceuticals, explosives, gelling agents, surface coatings, resins,and oxidation inhibitors by condensing aminoaromatic compounds withcarbohydrates or with carbohydrate derivatives.

One embodiment of this invention relates to a process which comprisescondensing an aminoaromatic compound with a carbohydrate in the presenceof a hydrogen fluoride catalyst to produce a compound selected from thegroup consisting of an aminoaryl-desoxy-alditol and anaminoaryl-desoxy-ketitol, and recovering said resultant condensationproduct.

A specific embodiment of this invention relates to a process whichcomprises condensing aniline with glucose in the presence of a hydrogenfluoride catalyst to produce a l-(aminophenyl)-l-desoxy-glucitol, andrecovering said resultant condensation product.

I have found that useful water-insoluble condensation products and alsowater-soluble condensation products are formed by reacting anaminoaromatic compound with carbohydrates and related substances in thepresence of a hydrogen fluoride catalyst. These reactions may be carriedout in steel equipment or other suitable apparatus lined with silver,copper, and certain alloys such as Monel metal and the like. Thistreatment may be effected at temperatures of from about 40 to about 100C. and preferably at temperatures of from about to about +50 C. Thepressure at which the reaction is carried out will vary with thereaction temperature used and the mol fractions of reactants andhydrogen fluoride catalyst present. While many of the condensationreactions are carried out at substantially atmospheric pressure, it maybe desirable in certain instances and with certain reactants to carryout the reaction at pressures up to about 100 atmospheres or more. It isconvenient in most instances to operate the equipment utilized at thepressure generated by the reaction mixture and the catalyst containedtherein.

Aromatic amines which may be used as starting materials in the processof this invention include aniline, methylaniline, dimethylaniline,diethylaniline, ortho-toluidine, para-toluidine, ortho-nitroaniline,meta-nitroaniline, para-nitroam'line, 2,4-dinitroaniline,ortho-phenylenediamine, meta-phenylenediamine, para-phenylenediamine,ortho-anisidine, para-anisidine, para-phenetidine, ortho-chloroaniline,meta-chloroaniline, para-chloroani- 2 line, para-bromoaniline,2,4,6-trichloroaniline, 2,4,6-tribromoaniline, diphenylamine,triphenylamine, ortho-tolidine, ortho-dianisidine, alpha-naphthylamine,beta-naphthylamine, etc.

Carbohydrates which are condensed with aminoal'omatic compounds to forma compound selected from the group consisting of anaminoaryl-desoXy-alditol and an aminoaryl-desoxy-ketitol include simplesugars, their desoxyand omega-carboxy derivatives, compound sugars oroligosaccharides, and polysaccharides.

Simple sugars include dioses, trioses, tetroses, pentoses, hexoses,heptoses, octoses, nonoses, and decoses. Compound sugars includepolysaccharides composed of only one type of sugar residue,polysaccharides composed of more than one type of sugar unit,polysaccharides composed of one type of uronic acid unit, i.e.,polyuronides, polysaccharides composed of aldose (pentose or hexose) anduronic acid units, polysaccharides containing hexose units esterifiedwith an inorganic acid, and polysaccharides containing amino sugarunits.

Utilizable simple sugars include the diose, glycolaldehyde, trioses,such as glycerylaldehyde and s-dihydroxyacetone; tetroses, such aserythrose, threose, erythrulose, and apiose; the pentoses, such asarabinose, xylose, ribose, lyxose, rhamnose (a methylpentose), fucose (amethylpentose), rhodeose (a methylpentose), digitalose (amethoxymethylpentose), ketoxylose (a ketopentose), 2-desoxyribose and2-desoxy-methylpentose(digitoxose); hexoses, such as mannose, glucose,idose, gulose, galactose, talose, allose, fructose, sorbose, tagatose,and psicose; heptoses, such as glucoheptose, mannoheptose,galactoheptose, sedoheptose, mannoketoheptose, glucoheptulose, andperseulose; octoses, such as glucooctose, mannooctose, andgalactooctose; nonoses, such as glucononose, and mannononose; anddecoses such as glucodecose. Desoxy derivatives of simple sugars areformed by the replacement of a hydroxyl substituent in a sugar withhydrogen thereby forming a methyl or methylene linkage. Thedesoxypentoses and desoxyhexoses are the most commonly occurring of suchcompounds. The omega-carboxy derivatives of simple sugars, which aresuitable in the process of the present invention include tartronicsemi-aldehyde or its tautomer, hydroxypyruvic acid;alpha-gamma-dihydroxyacetoacetic acid, threuronic acid,4-keto-2,3,S-trihydroxypentanoic acid, xyluronic acid,S-keto-tetrahydroxyhexanoic acids such as S-ketoallonic acid,S-keto-gluconic acid, S-keto-mannonic acid, S-keto-glllonic acid, andS-keto-galactonic acid; uronic acids containing 6 carbon atoms such asglucuronic acid, mannuronic acid, and galacturonic acid, and the6-ketopentahydroxy-heptanoic acids. The simple sugars and theiromega-carboxy derivatives, as starting materials for the process of thisinvention, may be represented by the following general formula:

(CHOH).

the compound is alpha-gamma-dihydroxyacetoacetic acid;

biose, sucrose, trehalose.

when A=H, 11:2, and B=CH2OH, the compound is and B=CH OH, the compoundis riboketose or xyloketose; when A=CH OH, n=2, and B=COOH, the compoundis a 4-keto-2,3,5-trihydroxypentanoic acid; when A=H, 11:3, and B=CH OH,the compound is ribose, arabinose, xylose or lyxose, when A=H, 11:3, andB=COOH, the compound is a 5 carbon atom uronic acid such as xyluronicacid; when A=CH OH, 11:3, and B=CH OH, the compound is psicose,fructose, sorbose, or tagatose; when A=CH OH, n=3, and B=COOH, thecompound is a 5-keto-tetrahydroxyhexanoic acid; when A=H, n=4, and B=CHOH, the compound is allose, altruose, glucose, mannose, gulose, idose,galactose, or talose; when A=H, n=4, and B=COOH, the compound is a 6carbon atom uronic acid such as glucuronic acid, mannuronic acid, andgalacturon'ic acid; when A=CH OH, n=4, and B=CH OH, the compounds areheptoses; and when A=CH OH, n=4, and B=COOH,

the compounds are 6-keto-penta-hydroxyheptanoic acids.

The utilizable oligosaccharides or compound sugars include disaccharidessuch as the pentose-hexose disaccharides including glucoapiose,vicianose and primeverose; the methyl-pentose-hexose disaccharidesincluding glycorhamnoside, and rutinose; and the dihexoses such asturanose, maltose, lactose, cellobiose, gentiobiose, meli- Otherutilizable compound sugars are represented by trisaccharides such as themethylpentose-hexose saccharides including rhamniose and robinose; thetrihexose saccharides including ratfinose, rnelezitose, and gentianose.An example of a suitable tetrasaccharide is stachyose.

Various polysaccharides are also utilizable in the process of thepresent invention. These polysaccharides include pentosans such asaraban, methylpentosans such as fucosan, and hexosans such as starch,cellulose, glycogen, inulin, mannan, galactan, lichenin, lcvan, dextran,and laminarin. Other polysaccharides which are composed of more than onetype of sugar unit such as pentosans like araboxylan, and the hexosanslike galactomannan may be used. Other utilizable polysaccharides arerepresented by those composed of uronic acid units and aldose units suchas gum arabic, damson gum, gum tragacanth, linseed mucilage, pectins,those composed of uronic acid units such as pectic acid and alginicacid, and those containing hexose units esterified with an inorganicacid such as certain seaweed polysaccharides like agar.

The hydrogen fluoride catalyst which is used in this process may be usedin anhydrous form or diluted With water to make a hydrofluoric acid ofthe desired concentration. The hydrofluoric acid may also be furtherdiluted with various inert diluents when it is desirable to operate theprocess of this invention with low hydrogen fluoride concentrations.Suitable inert diluents include the perfluoro derivatives ofn-paraflinic hydrocarbons such as perfluoro-propane, perfluoro-n-butane,perfluoron-pentane, perfluoro-n-hexane, etc. Other suitable diluents arewell known to those skilled in the art, for example, cycloparaffins suchas cyclopentane or cyclohexane may be utilized. In some instances,hydrofluoric acid of from about 85 to about 100% HP concentration isdesirable, and in some other instances it is most desirable to useanhydrous hydrogen fluoride as the catalyst.

The process may be carried out by slowly adding a hydrogen fluoridecatalyst to a stirred mixture of aminoaromatic compound and carbohydrateor related materialbeing subjected to reaction while maintaining thereaction temperature at from about -40 to about 100 C. by suitablecooling and/ or heating means. It is often desirable or advisable tocommingle the reactants and catalyst at relatively low temperatures suchas from about -80 C. to about 30 C. and then topermit the reactionmixture to warm gradually while the reactants and catalyst are stirredby suitable means such as a motor-driven stirrer or other adequatemixing equipment. After the reaction has reached the desired degree ofcompletion, the hydrogen fluoride catalyst is removed from the reactionmixture by distillation at atmospheric or lower pressures, or by passingan inert gas through the reaction mixture while maintaining it at arelatively low temperature. Also the entire reaction mixture andcatalyst may be mixed with water or may be added to ice in order toquench the activity of the hydrogen fluoride catalyst and to permitseparation of the organic reaction products and unreacted startingmaterials from the catalyst. The organic reaction products may also beseparated from aqueous hydrogen fluoride by means of an organic solventsuch as ether, in which some of the organic material may be dissolved.Further means of isolating the reaction products are illustrated in theexamples. Thus the product formed by reacting aniline with glucose orcellulose in the presence of substantially anhydrous hydrogen fluorideat 30 C. separated into an ether-soluble and water-insoluble product andan ether-insoluble and water-soluble product.

The process of this invention broadly emphasizes the reaction ofcarbohydrates including simple sugars, their derivatives, compoundsugars, and polysaccharides with aminoaromatic compounds using as acatalyst hydrogen fluoride. The type of product obtained is markedlyaffected by the length of time that the reactants are in contact withthe hydrogen fluoride catalyst as well as the temperature of thereaction. The reaction products of this process lead to materials havingdiversified uses. For example, some of the reaction products can be usedper se as surface coating materials as, for example, thermo'settingresins which can be prepared by heating. Resins can also be made byheating the reaction products with formaldehyde, urea, phenol, etc., andcombinations of the above enumerated compounds. Nitration of many of thereaction products will give explosives. These explosives will containnitro groups attached to the aromatic rings as well as being nitric acidesters or nitroalcohol derivatives. Various reaction products areeffective for gelling paraffinic or aromatic hydrocarbons. The productsare useful intermediates in the preparation of other organic compounds,for example, they may be reductively alkylated with an organic compoundcontaining a carbonyl group in the presence of hydrogen and suitablecatalyst. The nature of this invention is illustrated further by thefollowing examples, which however, should not be construed to limitunduly the generally broad scope of this invention.

Example I I I This example illustrates the reaction of aniline with acarbohydrate, namely, cellulose. Cellulose is a polysaccharidecontaining glucoside linkages and with all but one of the potentialaldehyde groups of the glucose residues involved in these glucosides.

As anexample of the manner of conducting these experiments, thefollowing detailed description is given: In a one liter steel turbomixerautoclave is sealed 41 grams of cellulose and '60 grams of aniline. Withstirring, the autoclave is then cooled to, -78 C. and about 220 grams ofhydrogen fluoride is added. The initial portion of the hydrogen fluorideis added slowly since the neutralization of the aniline with theequivalent amount of hydrogen fluoride is highly exothermic. After theaddition of the hydrogen fluoride is completed, the temperature isallowed to rise to 0 C. and the reactants are then contacted at thistemperature for 36 hours. Then, a stream of nitrogen is passed throughthe reactor at room temperature to remove most of the hydrogen fluoride.A substantial amount of hydrogen fluoride remains, although most of itcan be removed by prolonging the nitrogen purge. The autoclave is openedand the product is found to be a heavy fuming red-brown syrup. This isthen poured into a silver dish and, depending upon the amount ofhydrogen fluoride remaining therein, weighs from about 110 to about 130grams. After standing for several days in a hood-draft, the product ismascerated with large quantities of water. Then, the total product isplaced in a stirred flask and the product carefully neutralized to a pHof 7. The product is then mascerated again with cold water to removeinorganic fluorides. The cold water insoluble portion of the product istreated with boiling water which after cooling and reduction in volumeyields a chemical individual corresponding to1,l-di-(aminophenyl)-1-desoxy-glucitol of the following formula:

HIN NH:

Ii! CHOH CHOH CHOH

HOE

CHzOH Example II This experiment again illustrates the reaction of acarbohydrate, namely glucose, with an aminoaromatic compound. In thisexample 40 grams of glucose, 60 grams of aniline, and about 225 grams ofhydrogen fluoride are utilized. The present procedure is the same asthat described hereinabove in Example I down through allowing theproduct to stand in a draft. To this crude product is added one liter ofethyl ether and the mixture is allowed to stand for two days. The etheris then decanted ofi and the residue is dissolved in hot water andcarefully neutralized to a pH of 7. The water is then removed byevaporation and the residue mascerated with several batches of coldwater to remove inorganic fluorides. The product is again dissolved inhot water, is filtered while hot, and after cooling is allowed to standat 0 C. The crystals which separate at this point are identified andcorrespond to the 1,1-di-(aminophenyl)-1- desoxy-glucitol described inExample I.

The more soluble portion of the product is believed to containmono-aminophenyl-glucitol corresponding to the following structuralformula:

HsN

HsOH

Example III In this example, ortho-toluidine is reacted with glucose,The experiment is carried out in a steel turbomixer autoclave asdescribed in Example I, the charge being 69 grams of ortho-toluidine, 40grams of glucose, and about 225 grams of hydrogen fluoride. Theortho-toluidine and glucose are sealed into the autoclave which is thencooled to about 30 C. at which temperature the hydrogen fluoride isadded. The temperature of the autoclave is then allowed to rise to roomtemperature and is kept there for 12 hours during which time the mixtureis stirred. Then, while continuing the stirring, a stream of nitrogen ispassed through the autoclave for about 3 hours. The reaction product iswashed with several portions of cold water. The remaining product isdissolved in hot water,

6 is filtered, and this filtrate is then set aside to cool. Afterstanding for about 24 hours at about 0 C., crystals of a chemicalindividual are recovered therefrom. This material afterrecrystallization is found to have the following structural formula:

CHI OH:

NH: HIN

l (anon HOE HOH

HOE EHsOH Example IV In this example, starch is reacted withalpha-aminonaphthalene. This experiment is carried out in a steelturbomixer autoclave as described in Example I, the charge being 92grams of alpha-aminonaphthalene, 40 grams of starch, and about 220 gramsof hydrogen fluoride. The alpha-aminonaphthalene and starch are sealedinto the autoclave which is then cooled to about 40 C. at whichtemperature the hydrogen fluoride is added. The temperature of theautoclave is then allowed to rise to room temperature and is kept therefor 24 hours time during which time the reaction mixture is stirredcontinually. Then, a stream of nitrogen is passed through the autoclavefor about 6 hours. The reaction product is washed with several portionsof water, then steamed distilled to remove any unreactedalpha-aminonapththalene. The hot aqueous solution remaining in the steamdistilling flask was filtered, cooled, and set aside at 0 C. From thiscooled filtrate a new chemical entity is recovered. After neutralizationand recrystallization, a product is isolated of the following structuralformula:

HOH JJHOH HOH HOH HIOH I claim as my invention:

1. A process which comprises reacting an aminoaromatic compound selectedfrom the group consisting of aniline, ring substituted lower alkyl,nitro, amino, methoxy, ethoxy and halo aniline, and naphthylamine With acarbohydrate selected from the group consisting of monosaccharides,oligosaccharides, and polysaccharides, in the presence of hydrogenfluoride catalyst at a temperature of from about -40 C. to about C.

2. A process which comprises reacting aniline with cellulose in thepresence of hydrogen fluoride catalyst at a temperature of from about 40C. to about 100 C.

3. A process which comprises reacting aniline with glucose in thepresence of hydrogen fluoride catalyst at a temperature of from about 40C. to about 100 C.

4. A process which comprises reacting ortho-toluidine with glucose inthe presence of hydrogen fluoride catalyst at a temperature of fromabout -40 C. to about 100 C.

5. A process which comprises reacting alpha-aminonaphthalene with starchin the presence of hydrogen fluo- 7 8 ride catalyst at -'a temperatureof from abcut *40' C. 2,798,079 v July 2, 1957 to about 100 C.

OTHER REFERENCES References Cited In the file Hackhs ChemicalDictionary, p. 260, 3rd Ed., The

UNITED STATES PATENTS I Blakiston C0., Philadelphia (1944).

2,252,725 Niederl Aug. 19, 1941

1. A PROCESS WHICH COMPRISES REACTING AN AMINOAROMATIC COMPOUND SELECTEDFROM THE GROUP CONSISTING OF ANILINE, RING SUBSTITUTED LOWER ALKYL,NITRO, AMINO, METHOXY, ETHOXY AND HALO ANILINE, AND NAPHTHALAMINE WITH ACARBOHDRATE SELECTED FROM THE GROUP CONSISTING OF MONOSACCHARIDES,OLIGOSACCHARIDES, AND POLYSACCHARIDES, IN THE PRESENCE OF HYDROGENFLUORINE CATALYST AT A TEMPERATURE OF FROM ABOUT -40*C. TO ABOUT 100*C.